This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The Newgard laboratory uses interdisciplinary approaches for the study of the biochemical and molecular mechanisms involved in glucose-stimulated insulin secretion, including development of novel cellular models, gene discovery and genetic engineering. The overarching goal of this program project grant (PPG) continues to be the development of novel therapies for type 2 diabetes. The program has evolved from its genesis in 1999 as a collaboration between three research Centers within the University of Texas Southwestern Medical Center in Dallas (UTSWMC) to its current format, involving collaboration of four Centers located at UTSWMC and Duke University Medical Center. The program will continue with its unique format of melding projects on diabetes mechanisms with projects focused on development of new technologies for studying and treating the disease. In the past funding cycle, the most compelling advances have occurred in the area of pancreatic islet biology and related technologies.